Cysteine engineered anti-TENB2 antibodies and antibody drug conjugates

摘要

Cysteine engineered anti-TENB2 antibodies are engineered by replacing one or more amino acids of a parent anti-TENB2 antibody with non cross-linked, reactive cysteine amino acids. Methods of design, preparation, screening, and selection of the cysteine engineered anti-TENB2 antibodies are provided. Cysteine engineered anti-TENB2 antibodies (Ab) are conjugated with one or more drug moieties (D) through a linker (L) to form cysteine engineered anti-TENB2 antibody-drug conjugates having Formula I:
Ab-(L-D)p  Iwhere p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.

主权项

1. A cysteine engineered anti-TENB2 antibody comprising a heavy and a light chain, one or more free cysteine amino acid residues located in the heavy chain, and the sequence:Sequence near SequentialKabat Seq. Cys mutationNumberingNumberingI.D.VTVSSCSTKGPA121CA114C12 in combination with one or more additional cysteine mutations in the heavy chain, selected from the group consisting of:Sequence near SequentialKabat Seq. Cys mutationNumberingNumberingI.D.DVQLCESGPGQ5CQ5C 8LSLTCCVSGYSA23CA23C 9VSSASCKGPSVT123CT116C13WYVDGCEVHNAV285CV278C14 KGFYPCDIAVES378CS371C15   PPVLDCDGSFFS403CS396C 16.